Leukocyte filter and method

ABSTRACT

There is provided a leukocyte filter comprising: a prefilter portion; and a membrane filter portion downstream of the prefilter portion, the membrane filter portion having a pore size distribution having a median pore size between 3 and 12 microns and having at least 40% of the pore volume being constituted by pores having a pore cross section diameter of between 3 and 10 microns and having at least 5% of the pore volume being constitutted by pores having a pore cross section diameter larger than 10 microns. In a preferred embodiment, no more than 60% of the pore volume is constituted by pores having a pore cross section diameter larger than 10 microns. In another preferred embodiment, the membrane filter portion is characterized in that no more than 30% of the pore volume is constituted by pores having a pore cross section diameter less than 3 microns. In a preferred embodiment, the membrane filter portion is characterized in that no more than 30% of the pore volume is constituted by pores having a pore cross section diameter less than 3 microns. There is also provided a filtering method and a filtered blood product, including a filtered whole blood product.

FIELD OF THE INVENTION

[0001] The present invention relates to leukocyte filters and filtrationgenerally.

BACKGROUND OF THE INVENTION

[0002] Filters are commonly used to remove leukocytes from blood andblood products in order to minimize various adverse effects of whitecell transfusion. Examples of adverse effects include non-hemolyticfebrile reaction, alloimmunization and graft versus host disease.Commercial leukoreduction filters are mostly composed of non-wovenmaterials, which are made up of discrete fibers bonded or pressedtogether.

[0003] Another filter known in the art is a membrane filter, which,instead of having discrete fibers, is a continuous structure containinga network of pores. The membrane enables efficient capture of leukocytesand a reasonably good passage of the desired blood components (e.g.,erythrocytes, platelets or plasma). However, membrane filters known inthe art arc either lacking in performance or require specific materialsof construction, unusual pore morphology, a very narrow pore sizedistribution or pore size gradation within the filter.

[0004] One example of a membrane filter is described in U.S. Pat. No.5,895,575 assigned to the present applicant/assignee, the disclosure ofwhich is incorporated herein by reference. The '575 patent describes afilter composed of nitrocellulose membranes and non-woven materials.

[0005] U.S. Pat. No. 5,476,587 (Kuroki et al.) describes a membrane witha most frequent pore diameter of 1-5 μm, and a pore size weight averageto number average ratio of 1.5 to 2.5, the ratio gradually changing fromthe top to the bottom of the filter.

[0006] U.S. Pat. No. 5,707,526 (a continuation-in-part of Kuroki etal.'s '587 patent) describes a membrane having a most frequent porediameter of 1-5 μm, and a specific dust permeability, enclosed in ahousing of a specially designed structure.

[0007] U.S. Pat. No. 5,478,470 (Fukuda et al.) describes membranes witha specific set of properties, including pores of 2-30 μm having acombined pore volume equal to or greater than 94% of the total porevolume.

[0008] U.S. Pat. No. 5,665,233 (a division of Fukuda et al.'s '470patent) describes the use of porous materials, including membranes,having a specific set of properties, among them certain pore volumes,pore size gradation, leukocyte retention per layer, and layer thicknessof less than 0.5 mm.

[0009] European Patent Application Publication No. 0406,485 A1 (nowabandoned) describes membrane containing filters, wherein the membranesare strongly asymmetric, having a median pore size at the upstreamsurface substantially larger than at the downstream surface.

[0010] Japanese Patent Application No. 526,2656 describes membranes witha negative charge. Japanese Patent Application No. 503,4337 describesmembranes made specifically of polyvinyl formal or polyurethane.Japanese Patent Application No. 514,8150 describes a filter containingboth porous materials and a non-woven fabric with fibers of 0.8-3 μmdiameter. Japanese Patent Application No. 54-44270 (filed Apr. 13, 1979)describes a polyester foam used to trap leukocytes.

[0011] Other membrane filters are described in European PatentPublication No. 408,462 B1 and U.S. Pat. No. 5,234,593, both of whichhave unusual pore structures, and in U.S. Pat. Nos. 4,985,153 and5,783,094. The disclosures of all publications mentioned in the presentspecification are incorporated herein by reference.

[0012] In general in the prior art, membrane filters are constructed ofspecialized or non-commercial materials with narrow ranges of poresizes. In addition, the filters generally have a non-homogeneous porestructure throughout their bulk, i.e. they employ membranes wherein thepores of the membranes have large diameter on one side of the membraneand a narrower diameter on the other side. Also, it has been assumed inthe prior art that in order to obtain good throughput and prevent filterclogging, the filter must have a multilayer structure with a gradualdecrease in pore size in the (direction or flow.

SUMMARY OF THE INVENTION

[0013] The present invention seeks to provide an improved leukocytefilter, a filtering method and a filtered blood product, including afiltered whole blood product.

[0014] There is thus provided in accordance with a preferred embodimentof the present invention a leukocyte filter comprising: a prefilterportion; and a membrane filter portion downstream of the prefilterportion, the membrane filter portion having a pore size distributionhaving a median pore size between 3 and 12 microns and having at least40% of the pore volume being constituted by pores having a pore crosssection diameter of between 3 and 10 microns and having at least 5% ofthe pore volume being constituted by pores having a pore cross sectiondiameter larger than 10 microns.

[0015] In accordance with a preferred embodiment of the invention, nomore than 60% of the pore volume is constituted by pores having a porecross section diameter larger than 10 microns. In accordance with apreferred embodiment of the invention, the membrane filter portion ischaracterized in that no more than 30% of the pore volume is constitutedby pores having a pore cross section diameter less than 3 microns. Inaccordance with a preferred embodiment of the invention, the membranefilter portion is characterized in that no more than 30% of the porevolume is constituted by pores having a pore cross section diameter lessthan 3 microns.

[0016] There is also provided, in accordance with a preferred embodimentof the invention, a leukocyte filter comprising: a prefilter portion;and a membrane filter portion downstream of the prefilter portion, theprefilter portion being characterized in that it captures less than 60%of incoming leukocytes; and the membrane filter portion beingcharacterized in that non-cellulosic and generally homogeneous. Inaccordance with a preferred embodiment of the invention, the membranefilter portion is characterized in that it has a pore surfacearea/membrane volume ratio larger than 6 square meters per milliliter ofmembrane volume. In accordance with a preferred embodiment of theinvention, the membrane filter portion is characterized in that it has apore surface area/membrane mass ratio larger than 12 square meters pergram of membrane. In accordance with a preferred embodiment of theinvention, the membrane filter portion comprises at least one layer of agenerally homogeneous non-cellulosic membrane, wherein the total porevolume of pores having a diameter between 1-30 microns is less than 90%of the total pore volume. In accordance with a preferred embodiment ofthe invention, the membrane filter portion is characterized in that ithas a pore size distribution having a median pore size between 3 and 12microns and having at least 40% of the pore volume being constituted bypores having a pore cross section diameter of between 3 and 10 micronsand having at least 5% of the pore volume being constituted by poreshaving a pore cross section diameter larger than 10 microns. Inaccordance with a preferred embodiment of the invention, no more than60% of the pore volume is constituted by pores having a pore crosssection diameter larger than 10 microns. In accordance with a preferredembodiment of the invention, the membrane filter portion ischaracterized in that at least 40% of its pore volume is constituted bypores having a pore cross section diameter of between 3 and 10 microns.In accordance with a preferred embodiment of the invention, the membranefilter portion is characterized in that at least 5% of the pore volumeis constituted by pores having a pore cross section diameter larger than10 microns. In accordance with a preferred embodiment of the invention,the membrane filter portion is characterized in that no more than 30% ofthe pore volume being constituted by pores having a pore cross sectiondiameter less than 3 microns. In accordance with a preferred embodimentof the invention, the membrane filter portion is characterized in thatit has a pore size distribution having a median pore size between 3 and12 microns and having at least 40% of the pore volume being constitutedby pores having a pore cross section diameter of between 3 and 10microns and having at least 5% of the pore volume being, constituted bypores having a pore cross section diameter larger than 10 microns.

[0017] There is also provided, in accordance with a preferred embodimentof the invention, a leukocyte filter comprising: a prefilter portion;and a membrane filter portion downstream of the prefilter portion, saidmembrane filter portion being characterized in that it has a poresurface area/membrane volume ratio larger than 6 square meters permilliliter of membrane volume. In accordance with a preferred embodimentof the invention, the membrane filter portion is characterized in thatthe cumulative surface area of pores having a pore diameter of 2-30microns is less than 30% of the total surface area of the membrane. Inaccordance with a preferred embodiment of the invention, the membranefilter portion is characterized in that it has a more surfacearea/membrane mass ratio larger than 12 square meters per gram ofmembrane. In accordance with a preferred embodiment of the invention,the membrane filter portion comprises at least one layer of a generallyhomogeneous non-cellulosic membrane, wherein the total pore volume ofpores having a diameter between 1-30 microns is less than 90% of thetotal pore volume. In accordance with a preferred embodiment of theinvention, the membrane filter portion comprises at least one layer of agenerally homogeneous non-cellulosic membrane, wherein the total porevolume of pores having a diameter between 1-30 microns is less than 90%of the total pore volume. In accordance with a preferred embodiment ofthe invention, the membrane filter portion is characterized in that ithas a pore size distribution having a median pore size between 3 and 12microns and having at least 40% of the pore volume being constituted bypores having a pore cross section diameter of between 3 and 10 micronsand having at least 5% of the pore volume being constituted by poreshaving a pore cross section diameter larger than 10 microns. Inaccordance with a preferred embodiment of the invention, no more than60% of the pore volume is constituted by pores having a pore crosssection diameter larger than 10 microns. In accordance with a preferredembodiment of the invention, the membrane filter portion ischaracterized in that at least 40% of its pore volume is constituted bypores having a pore cross section diameter of between 3 and 10 microns.In accordance with a preferred embodiment of the invention, the membranefilter portion is characterized in that at least 5% of the pore volumeis constituted by pores having a pore cross section diameter larger than10 microns. In accordance with a preferred embodiment of the invention,the membrane filter portion is characterized in that no more than 30% ofthe pore volume being constituted by pores having a pore cross sectiondiameter less than 3 microns. In accordance with a preferred embodimentof the invention, the membrane filter portion is characterized in thatit has a pore size distribution having a median pore size between 3 and12 microns and having at least 40% of the pore volume being constitutedby pores having a pore cross section diameter of between 3 and 10microns and having at least 5% of the pore volume being constituted bypores having a pore cross section diameter larger than 10 microns.

[0018] There is also provided in accordance with a preferred embodimentof the invention a leukocyte filter comprising: a prefilter portion; anda membrane filter portion downstream of the prefilter portion, saidmembrane filter portion being characterized in that it has a poresurface area/membrane mass ratio larger than 12 square meters per gramof membrane.

[0019] There is also provided in accordance with a preferred embodimentof the invention, the a leukocyte filter comprising: a prefilterportion; and a membrane filter portion downstream of the prefilterportion, said membrane filter portion comprising at least one layer of agenerally homogeneous non-cellulosic membrane, wherein the total porevolume of pores having a diameter between 1-30 microns is less than 90%of the total pore volume. In accordance with a preferred embodiment ofthe invention, the membrane filter portion is characterized in that ithas a pore size distribution having a median pore size between 3 and 12microns and having at least 40% of the pore volume being constituted bypores having a pore cross section diameter of between 3 and 10 micronsand having at least 5% of the pore volume being constituted by poreshaving a pore cross section diameter larger than 10 microns. Inaccordance with a preferred embodiment of the invention, no more than60% of the pore volume is constituted by pores having a pore crosssection diameter larger than 10 microns. In accordance with a preferredembodiment of the invention, the membrane filter portion ischaracterized in that at least 40% of its pore volume is constituted bypores having a pore cross section diameter of between 3 and 10 microns.In accordance with a preferred embodiment of the invention, the membranefilter portion is characterized in that at least 5% of the pore volumeis constituted by pores having a pore cross section diameter larger than10 microns. In accordance with a preferred embodiment of the invention,the membrane filter portion is characterized in that no more than 30% ofthe pore volume is constituted by pores having a pore cross sectiondiameter less than 3 microns. In accordance with a preferred embodimentof the invention, the membrane filter portion is characterized in thatat least 40% of its pore volume is constituted by pores having a porecross section diameter of between 3 and 10 microns. In accordance with apreferred embodiment of the invention, the membrane filter portion ischaracterized in that at least 5% of the pore volume is constituted bypores having a pore cross section diameter larger than 10 microns. Inaccordance with a preferred embodiment of the invention, the membranefilter portion is characterized in that no more than 30% of the porevolume is constituted by pores having a pore cross section diameter lessthen 3 microns.

[0020] There is also provided in accordance with a preferred embodimentof the invention, a leukocyte filter comprising: a prefilter portion;and a membrane filter portion downstream of the prefilter portion, saidmembrane filter portion having at least 40% of its pore volume beingconstituted by pores having a pore cross section diameter of between 3and 10 microns. In accordance with a preferred embodiment of theinvention the membrane filter portion is characterized in that at least5% of the pore volume is constituted by pores having a pore crosssection diameter larger than 10 microns. In accordance with a preferredembodiment of the invention, the membrane filter portion ischaracterized in that no more than 30% of the pore volume is constitutedby pores having a pore cross section diameter less than 3 microns. Inaccordance with a preferred embodiment of the invention, the membranefilter portion is characterized in that no more than 30% of the porevolume is constituted by pores having a pore cross section diameter lessthan 3 microns.

[0021] There is also provided in accordance with a preferred embodimentof the invention a leukocyte filter comprising: a prefilter portion; anda membrane filter portion downstream of the prefilter portion, saidmembrane filter portion having at least 5% of the pore volume beingconstituted by pores having a pore cross section diameter larger than 10microns.

[0022] There is also provided in accordance with a preferred embodimentof the invention a leukocyte filter comprising: a prefilter portion; anda membrane filter portion downstream of the prefilter portion, saidmembrane filter portion having no more than 30% of the pore volume beingconstituted by pores having a pore cross section diameter less than 3microns.

[0023] There is also provided in accordance with a preferred embodimentof the invention a leukocyte filtering method comprising supplying ablood product to be filtered of leukocytes to a prefilter which capturesless than 60% of incoming leukocytes; and supplying prefiltered bloodproduct to a non-cellulosic and generally homogeneous membrane filter;wherein said blood product to be filtered of leukocytes has had thecontent of at least one blood component removed or reduced, relative tothe content of said at least one component in whole blood, prior to thestep of supplying the blood product to be filtered of leukocytes to theprefilter. In accordance with a preferred embodiment of the invention,the membrane filter is characterized in that it has a pore surfacearea/membrane volume ratio larger than 6 square meters per milliliter ofmembrane volume. In accordance with a preferred embodiment of theinvention, the membrane filter is characterized in that it has a poresurface area/membrane mass ratio larger than 12 square meters per gramof membrane. In accordance with a preferred embodiment of the invention,the membrane filter comprises at least one layer of a generallyhomogeneous non-cellulosic membrane, wherein the total pore volume ofpores having a diameter between 1-30 microns is less than 90% of thetotal pore volume. In accordance with a preferred embodiment of theinvention, the membrane filter is characterized in that it has a poresize distribution having a median pore size between 3 and 12 microns andhaving at least 40% of the pore volume being constituted by pores havinga pore cross section diameter of between 3 and 10 microns and having atleast 5% of the pore volume being constituted by pores having a porecross section diameter larger than 10 microns. In accordance with apreferred embodiment of the invention, no more than 60% of the porevolume is constituted by pores having a pore cross section diameterlarger than 10 microns. In accordance with a preferred embodiment of theinvention, the membrane filter is characterized in that at least 40% ofits pore volume is constituted by pores having a pore cross sectiondiameter of between 3 and 10 microns. In accordance with a preferredembodiment of the invention, the membrane filter is characterized inthat at least 5% of the pore volume is constituted by pores having apore cross section diameter larger than 10 microns. In accordance with apreferred embodiment of the invention, the membrane filter ischaracterized in that no more than 30% of the pore volume beingconstituted by pores having a pore cross section diameter less than 3microns. In accordance with a preferred embodiment of the invention, themembrane filter is characterized in that it has a pore size distributionhaving a median pore size between 3 and 12 microns and having at least40% of the pore volume being constituted by pores having a pore crosssection diameter of between 3 and 10 microns and having at least 5% ofthe pore volume being constituted by pores having a pore cross sectiondiameter larger than 10 microns.

[0024] There is also provided in accordance with a preferred embodimentof the invention a leukocyte filtering method comprising: supplying ablood product to be filtered of leukocytes to a prefilter; and supplyingprefiltered blood product to a membrane filter downstream of theprefilter, said membrane filter being characterized in that it has apore surface area/membrane volume ratio larger than 6 square meters permilliliter of membrane volume; wherein said blood product to be filteredof leukocytes has had the content of at least one blood componentremoved or reduced, relative to the content of said at least onecomponent in whole blood, prior to the step of supplying the bloodproduct to be filtered of leukocytes to the prefilter. In accordancewith a preferred embodiment of the invention, the membrane filter ischaracterized in that it has a pore surface area/membrane mass ratiolarger than 12 square meters per gram of membrane. In accordance with apreferred embodiment of the invention, the membrane filter comprises atleast one layer of a generally homogeneous non-cellulosic membrane,wherein the total pore volume of pores having a diameter between 1-30microns is less than 90% of the total pore volume. In accordance with apreferred embodiment of the invention, the membrane filter comprises atleast one layer or a non-cellulosic membrane, wherein the total porevolume of pores having a diameter between 1-30 microns is less than 90%of the total pore volume. In accordance with a preferred embodiment ofthe invention, the non-cellulosic membrane is a generally homogeneousmembrane. In accordance with a preferred embodiment of the invention,the membrane filter is characterized in that it has a pore sizedistribution having a median pore size between 3 and 12 microns andhaving at least 40% of the pore volume being constituted by pores havinga pore cross section diameter of between 3 and 10 microns and having atleast 5% of the pore volume being constituted by pores having a porecross section diameter larger than 10 microns. In accordance with apreferred embodiment of the invention, no more than 60% of the porevolume is constituted by pores having a pore cross section diameterlarger than 10 microns. In accordance with a preferred embodiment of theinvention, the membrane filter is characterized in that at least 40% ofits pore volume is constituted by pores having a pore cross sectiondiameter of between 3 and 10 microns. In accordance with a preferredembodiment of the invention, the membrane filter is characterized inthat at least 5% of the pore volume is constituted by pores having apore cross section diameter larger than 10 microns. In accordance with apreferred embodiment of the invention, the membrane filter ischaracterized in that no more than 30% of the pore volume is constitutedby pores having a pore cross section diameter less than 3 microns. Inaccordance with a preferred embodiment of the invention, the membranefilter is characterized in that it has a pore size distribution having amedian pore size between 3 and 12 microns and having at least 40% of thepore volume having constituted by pores having a pore cross sectiondiameter of between 3 and 10 microns and having at least 5% of the porevolume being constituted by pores having a pore cross section diameterlarger than 10 microns.

[0025] There is also provided in accordance with a preferred embodimentof the invention a leukocyte filtering method comprising: supplying ablood product to be filtered of leukocytes to a prefilter; and supplyingprefiltered blood product to a membrane filter downstream of theprefilter, said membrane filter being characterized so that it has apore surface area/membrane mass ratio larger than 12 square meters pergram of membrane; wherein said blood product to be filtered ofleukocytes has had the content of at least one blood component removedor reduced, relative to the content of said at least one component inwhole blood, prior to the step of supplying the blood product to befiltered of leukocytes to the prefilter.

[0026] There is also provided in accordance with a preferred embodimentof the invention a leukocyte filtering method comprising: supplying ablood product to be filtered of leukocytes to a prefilter; and supplyingprefiltered blood product to a membrane filter comprising at least onelayer of a non-cellulosic membrane, wherein the total pore volume ofpores having a diameter between 1-30 microns is less than 90% of thetotal pore volume; wherein said blood product to be filtered ofleukocytes has had the content of at least one blood component removedor reduced, relative to the content of said at least one component inwhole blood, prior to the step of supplying the blood product to befiltered of leukocytes to the prefilter. In accordance with a preferredembodiment of the invention, the non-cellulosic membrane is a generallyhomogeneous membrane. In accordance with a preferred embodiment of theinvention, the membrane filter is characterized in that it has a poresize distribution having a median pore size between 3 and 12 microns andhaving at least 40% of the pore volume being constituted by pores havinga pore cross section diameter of between 3 and 10 microns and having atleast 5% of the pore volume being constituted by pores having a porecross section diameter larger than 10 microns. In accordance with apreferred embodiment of the invention, no more than 60% of the porevolume is constituted by pores having a pore cross section diameterlarger than 10 microns. In accordance with a preferred embodiment of theinvention, the membrane filter is characterized in that least 40% of itspore volume is constituted by pores having a pore cross section diameterof between 3 and 10 microns. In accordance with a preferred embodimentof the invention, the membrane filter is characterized in that at least5% of the pore volume is constituted by pores having a pore crosssection diameter larger than 10 microns. In accordance with a preferredembodiment of the invention, the membrane filter is characterized inthat no more than 30% of the pore volume is constituted by pores havinga pore cross section diameter less than 3 microns. In accordance with apreferred embodiment of the invention, the membrane filter ischaracterized in that at least 40% of its pore volume is constituted bypores having a pore cross section diameter of between 3 and 10 microns.In accordance with a preferred embodiment of the invention, the membranefilter is characterized in that at least 5% of the pore volume isconstituted by pores having a pore cross section diameter larger than 10microns. In accordance with a preferred embodiment of the invention, themembrane filter is characterized in that no more than 30% of the porevolume is constituted by pores having a pore cross section diameter lessthan 3 microns.

[0027] There is also provided in accordance with a preferred embodimentof the invention a leukocyte filtering method comprising: supplying ablood product to be filtered of leukocytes to a prefilter; and supplyprefiltered blood product to a membrane filter downstream of theprefilter, said membrane filter being characterized in that it has apore size distribution having a median pore size between 3 and 12microns and having at least 40% of the pore volume being constituted bypores having a pore cross section diameter of between 3 and 10 micronsand having at least 5% of the pore volume being constituted by poreshaving a pore cross section diameter larger than 10 microns; whereinsaid blood product to be filtered of leukocytes has had the content ofat least one blood component removed or reduced, relative to the contentof said at least one component i whole blood, prior to the step ofsupplying the blood product to be filtered of leukocytes to theprefilter. In accordance with a preferred embodiment of the invention,no more than 60% of the pore volume is constituted by pores having apore cross section diameter larger than 10 microns. In accordance with apreferred embodiment of the invention, the membrane filter ischaracterized in that at least 40% of its pore volume is constituted bypores having a pore cross section diameter of between 3 and 10 microns.In accordance with a preferred embodiment of the invention, the membranefilter is characterized in that at least 5% of the pore volume isconstituted by pores having a pore cross section diameter larger than 10microns. In accordance with a preferred embodiment of the invention, themembrane filter is characterized in that no more than 30% of the porevolume being constituted by pores having a pore cross section diameterless than 3 microns. In accordance with a preferred embodiment of theinvention, the membrane filter is characterized in that least 40% of itspore volume is constituted by pores having a pore cross section diameterof between 3 and 10 microns. In accordance with a preferred embodimentof the invention, the membrane filter is characterized in that at least5% of the pore volume is constituted by pores having a pore crosssection diameter larger than 10 microns. In accordance with a preferredembodiment of the invention, the membrane filter is characterized inthat no more than 30% of the pore volume being constituted by poreshaving a pore cross section diameter less than 3 microns. In accordancewith a preferred embodiment of the invention, the membrane filter ischaracterized in that at least 5% of the pore volume is constituted bypores having a pore cross section diameter larger than 10 microns. Inaccordance with a preferred embodiment of the invention, the membranefilter is characterized in that no more than 30% of the pore volume isconstituted by pores having a pore cross section diameter less than 3microns.

[0028] There is also provided in accordance with a preferred embodimentof the invention a leukocyte filtering method comprising: supplying, ablood product to be filtered of leukocytes to a prefilter; and supplyingprefiltered blood product to a membrane filter downstream of theprefilter, said membrane filter being characterized in that at least 40%of its pore volume is constituted by pores having a pore cross sectiondiameter of between 3 and 10 microns; wherein said blood product to befiltered of leukocytes has had the content of at least one bloodcomponent removed or reduced, relative to the content of said at leastone component in whole blood, prior to the step of supplying, the bloodproduct to be filtered of leukocytes to the prefilter. In accordancewith a preferred embodiment of the invention, the membrane filter ischaracterized in that at least 5% of the pore volume is constituted bypores having a pore cross section diameter larger than 10 microns. Inaccordance with a preferred embodiment of the invention, the membranefilter is characterized in that no more than 30% of the pore volume isconstituted by pores having a pore cross section diameter less than 3microns. In accordance with a preferred embodiment of the invention, themembrane filter is characterized in that no more than 30% of the porevolume is constituted by pores having a pore cross section diameter lessthan 3 microns. In accordance with a preferred embodiment of theinvention, the membrane filter is characterized in that it has a poresize distribution having a median pore size between 3 and 12 microns andhaving at least 40% of the pore volume being constituted by pores havinga pore cross section diameter of between 3 and 10 microns and having atleast 5% of the pore volume being constituted by pores having a porecross section diameter larger than 10 microns. In accordance with apreferred embodiment of the invention, the membrane filter ischaracterized in that no more than 30% of the pore volume is constitutedby pores having a pore cross section diameter less than 3 microns. Inaccordance with a preferred embodiment of the invention. The membranefilter is characterized in that it has a pore size distribution having amedian pore size between 3 and 12 microns and having at least 40% of thepore volume being constituted by pores having a pore cross sectiondiameter of between 3 and 10 microns and having at least 5% of the porevolume being constituted by pores having a pore cross section diameterlarger than 10 microns. In accordance with a preferred embodiment of theinvention, the membrane filter is characterized in that it has a poresize distribution having a median pore size between 3 and 12 microns andhaving at least 40% of the pore volume being constituted by pores havinga pore cross section diameter of between 3 and 10 microns and having atleast 5% of the pore volume being constituted by pores having a porecross section diameter larger than 10 microns.

[0029] There is also provided in accordance with a preferred embodimentof the invention a leukocyte filtering method comprising: supplying ablood product to be filtered of leukocytes to a prefilter; and supplyingprefiltered blood product to a membrane filter having at least 5% of itspore volume constituted by pores having a pore cross section diameterlarger than 10 microns; wherein said blood product to be filtered ofleukocytes has had the content of at least one blood component removedor reduced, relative to the content of said at least one component inwhole blood, prior to the step of supplying the blood product to befiltered of leukocytes to the prefilter.

[0030] There is also provided in accordance with a preferred embodimentof the invention a leukocyte filtering method comprising: supplyingprefiltered blood product to be filtered of leukocytes to a prefilter;and supplying prefiltered blood product to a membrane filter downstreamof the prefilter, said membrane filter being characterized in that nomore than 30% of its pore volume is constituted by pores having a porecross section diameter less than 3 microns; wherein said blood productto be filtered of leukocytes has had the content of at least one bloodcomponent removed or reduced, relative to the content of said at leastone component in whole blood, prior to the step of supplying the bloodproduct to be filtered of leukocytes to the prefilter.

[0031] There is also provided in accordance with a preferred embodimentof the invention a leukocyte filtered blood product produced by a methodincluding: supplying a blood product to be filtered of leukocytes to aprefilter which captures less than 60% of incoming leukocytes; andsupplying prefiltered blood product to a non-cellulosic and generallyhomogeneous membrane filter; wherein the leukocyte filtered bloodproduct has had the content of at least one blood component removed orreduced, relative to the content of said at least one component in wholeblood, prior to the step of supplying the blood product to be filteredof leukocytes to the prefilter. In accordance with a preferredembodiment of the invention, the membrane filter is characterized inthat it has a pore surface area/membrane volumes ratio larger than 6square meters per milliliter of membrane volume. In accordance with apreferred embodiment of the invention, the membrane filter ischaracterized in that it has a pore surface area/membrane mass ratiolarger than 12 square meters per gram of membrane. In accordance with apreferred embodiment of the invention, the membrane filter comprises atleast one layer of a generally homogeneous non-cellulosic membrane,wherein the total pore volume of pores having a diameter between 1-30microns is less than 90% of the total pore volume. In accordance with apreferred embodiment of the invention, the membrane filter ischaracterized in that it has a pore size distribution having a medianpore size between 3 and 12 microns and having at least 40% of the porevolume being constituted by pores having a pore cross section diameterof between 3 and 10 microns and having at least 5% of the pore volumebeing constituted by pores having a pore cross section diameter largerthan 10 microns. In accordance with a preferred embodiment of theinvention, no more than 60% of the pore volume is constituted by poreshaving a pore cross section diameter larger than 10 microns. Inaccordance with a preferred embodiment of the invention, the membranefilter is characterized in that at least 40% of its pore volume isconstituted by pores having a pore cross section diameter of between 3and 10 microns. In accordance with a preferred embodiment of theinvention, the membrane filter is characterized in that at least 5% ofthe pore volume is constituted by pores having a pore cross sectiondiameter larger than 10 microns. In accordance with a preferredembodiment of the invention, the membrane filter is characterized inthat no more than 30% of the pore volume is constituted by pores havinga pore cross section diameter than 3 microns.

[0032] There is also provided in accordance with a preferred embodimentof the invention a leukocyte filtered blood product produced by a methodcomprising: supplying a blood product to be filtered of leukocytes to aprefilter; and supplying prefiltered blood product to a membrane filterdownstream of the prefilter, said membrane filter being characterized inthat it has a pore surface area/membrane volume ratio larger than 6square meters per milliliter of membrane volume; wherein the leukocytefiltered blood product has had the content of at least one bloodcomponent removed or reduced, relative to the content of said at leastone component in whole blood, prior to the step of supplying the bloodproduct to be filter of leukocytes to the prefilter.

[0033] There is also provided in accordance with a preferred embodimentof the invention a leukocyte filtered blood product produced by a methodcomprising: supplying a blood product to be filtered of leukocytes to aprefilter; and supplying prefiltered blood product to a membrane filterdownstream of the prefilter, said membrane filter being characterized inthat it has a pore surface area/membrane mass ratio larger than 12square meters per gram of membrane; wherein the leukocyte filtered bloodproduct has had the content of at least one blood component removed orreduced, relative to the content of said at least one component in wholeblood, prior to the step of supplying the blood product to filtered ofleukocytes to the prefilter.

[0034] There is also provided in accordance with a preferred embodimentof the invention a leukocyte filtered blood product produced by a methodcomprising: supplying a blood product to be filtered of leukocytes to aprefilter; and supplying prefiltered blood product to a membrane filterdownstream of the prefilter, said membrane filter being characterized inthat it has a pore size distribution having a median pore size between 3and 12 microns and having at least 40% of the pore volume beingconstituted by pores having a pore cross section diameter of between 3and 10 microns and having at least 5% of the pore volume beingconstituted by pores having a pore cross section diameter larger than 10microns; wherein the leukocyte filtered blood product has had thecontent of at least one blood component removed or reduce, relative tothe content of said at least one component in whole blood, prior to thestep of supplying the blood product to be filtered of leukocytes to theprefilter.

[0035] There is also provided in accordance with a preferred embodimentof the invention a leukocyte filtered blood product produced by a methodcomprising: supplying a blood product to be filtered of leukocytes to aprefilter; and supplying prefiltered blood product to a membrane filterdownstream of the prefilter, said membrane filter being characterized inthat at least 40% of its pore volume is constituted by pores having apore cross section diameter of between 3 and 10 microns; wherein saidleukocyte filtered blood product has had the content of at least oneblood component removed or reduced, relative to the content of said atleast one component in whole blood, prior to the step of supplying theblood product to be filtered of leukocytes to the prefilter.

[0036] There is also provided in accordance with a preferred embodimentof the invention a leukocyte filtered blood product produced by a methodcomprising: supplying a blood product to be filtered of leukocytes to aprefilter; and supplying prefiltered blood product to a membrane filterhaving at least 5% of its pore volume constituted by pores having a porecross section diameter larger than 10 microns; wherein said leukocytefiltered blood product has had the content of at least one bloodcomponent removed or reduced, relative to the content of said at leastone component in whole blood, prior to the step of supplying the bloodproduct to be filtered of leukocytes to the prefilter.

[0037] There is also provided in accordance with a preferred embodimentof the invention a leukocyte filtered blood product produced by a methodcomprising: supplying a blood product to be filtered of leukocytes to aprefilter and supplying prefiltered blood product to a membrane filterdownstream of the prefilter, and membrane filter being characterized inthat no more than 30% of its pore volume is constituted by pores havinga pore cross section diameter less than 3 microns; wherein saidleukocyte filtered blood product has had the content of at least oneblood component removed or reduced, relative to the content of said atleast one component in whole blood, prior to the step of supplying theblood product to be filtered of leukocytes in the prefilter.

[0038] There is also provided, in accordance with a preferred embodimentof the invention, a leukocyte filtering method, comprising: supplyingwhole blood to a prefilter, and supplying prefiltered blood to amembrane filter downstream of the prefilter, said membrane filter beingcharacterized in that it comprises at least two non-cellulosic membraneshaving generally the same degree of symmetry and each having a thicknessof less than about 0.25 mm; characterized in that the prefilter andmembrane filter, operating together, reduce the number of leukocytespresent in one unit of whole blood to no more than five million. Inaccordance with a preferred embodiment of the invention, the prefilterand membrane filter, operating together reduce the number of leukocytespreset in one unit of whole blood to no more than one million. Inaccordance with a preferred embodiment of the invention, the filteredblood product also contains at least 60% of the platelets contained inthe whole blood before filtration and at least 85% of the red cellscontained in the whole blood before filtration.

[0039] There is also provided in accordance with a preferred embodimentof the invention a leukocyte filtering method comprising: whole blood toa prefilter which captures less than 60% of incoming leukocytes; andsupplying prefiltered whole blood in a non-cellulosic and generallyhomogeneous membrane filter. In accordance with a preferred embodimentof the invention, the membrane filter is characterized in that it has apore surface area/membrane volume ratio larger than 6 square meters permilliliter of membrane volume. In accordance with a preferred embodimentof the invention, the membrane filter is characterized in that it has apore surface area/membrane mass ratio larger than 12 square meters pergram of membrane. In accordance with a preferred embodiment of theinvention, the membrane filter comprises at least one layer of agenerally homogeneous non-cellulosic membrane, wherein the total porevolume of pores having a diameter between 1-30 microns is less than 90%of the total pore volume. In accordance with a preferred embodiment ofthe invention, the membrane filter is characterized in that it has apore size distribution having a median pore size between 3 and 12microns and having at least 40% of the pore volume being constituted bypores having a pore cross section diameter of between 3 and 10 micronsand having at least 5% of the pore volume being constituted by poreshaving a pore cross section diameter larger than 10 microns. Inaccordance with a preferred embodiment of the invention, no more than60% of the pore volume is constituted by pores having a pore crosssection diameter larger than 10 microns. In accordance with a preferredembodiment of the invention, the membrane filter is characterized inthat at least 40% ot its pore volume is constituted by pores having apore cross section diameter of between 3 and 10 microns. In accordancewith a preferred embodiment of the invention, the membrane filter ischaracterized in that at least 5% of the pore volume is constituted bypores having a pore cross section diameter larger than 10 microns. Inaccordance with a preferred embodiment of the invention, the membranefilter is characterized in that no more than 30of the pore volume beingconstituted by pores having a pore cross section diameter less than 3microns. In accordance with a preferred embodiment of the invention, themembrane filter is characterized in that it has a pore size distributionhaving a median pore size between 3 and 12 microns and having at least40% of the pore volume being constituted by pores having a pore crosssection diameter of between 3 and 10 microns and having at least 5% ofthe pore volume being constituted by pores having a pore cross sectiondiameter larger than 10 microns.

[0040] There is also provided in accordance with a preferred embodimentof the invention a leukocyte filtering method comprising: supplyingwhole blood to a prefilter; and supplying prefiltered whole blood to amembrane filter downstream of the prefilter, said membrane filter beingcharacterized in that it has a pore surface area/membrane volume ratiolarger than 6 square meters per milliliter of membrane volume. Inaccordance with a preferred embodiment of the invention, the membranefilter is characterized in that it has a pore surface area/membrane massratio larger than 12 square meters per gram of membrane. In accordancewith a preferred embodiment of the invention, the membrane filtercomprises at least one layer of a generally homogeneous non-cellulosicmembrane, wherein the total pore volume of pores having a diameterbetween 1-30 microns is less than 90% of the total pore volume. Inaccordance with a preferred embodiment of the invention, the membranefilter comprises at least one layer of a non-cellulosic membrane,wherein the total pore volume of pores having a diameter between 1-30microns is less than 90% of the total pore volume. In accordance with apreferred embodiment of the invention, the non-cellulosic membrane is agenerally homogeneous membrane. In accordance with a preferredembodiment of the invention, the membrane filter is characterized inthat it has a pore size distribution having a median pore size between 3and 12 microns and having at least 40% of the pore volume beingconstituted by pores having a pore cross section diameter of between 3and 10 microns and having at least 5% of the pore volume beingconstituted by pores having a pore cross section diameter larger than 10microns. In accordance with a preferred embodiment of the invention, nomore than 60% of the pore volume is constituted by pores having a porecross section diameter larger than 10 microns. In accordance with apreferred embodiment of the invention, the membrane filter ischaracterized in that at least 40% of its pore volume is constituted bypores having a pore cross section diameter of between 3 and 10 microns.In accordance with a preferred embodiment of the invention, the membranefilter is characterized in that at least 5% of the pore volume isconstituted by pores having a pore cross section diameter larger than 10microns. In accordance with a preferred embodiment of the invention, themembrane filter is characterized in that no more than 30% of the porevolume is constituted by pores having a pore cross section diameter lessthan 3 microns. In accordance with a preferred embodiment of theinvention, the membrane filter is characterized in that it has a poresize distribution having a median pore size between 3 and 12 microns andhaving at least 40% of the pore volume being constituted by pores havinga pore cross section diameter of between 3 and 10 microns and having atleast 5% of the pore volume being constituted by pores having a porecross section diameter larger than 10 microns.

[0041] There is also provided in accordance with a preferred embodimentof the invention a leukocyte filtering method comprising: supplyingwhole blood to a prefilter, and supplying prefiltered whole blood to amembrane filter downstream of the prefilter, said membrane filter beingcharacterized in that it has a pore surface area/membrane mass ratiolarger than 12 square meters per gram of membrane.

[0042] There is also provided in accordance with a preferred embodimentof the invention a leukocyte filtering method comprising: supplyingwhole blood to a prefilter; and supplying prefiltered whole blood to amembrane filter comprising at least one layer of a non-cellulosicmembrane, wherein the total pore volume of pores having a diameterbetween 1-30 microns is less than 90% of the total pore volume. Inaccordance with a preferred embodiment of the invention, thenon-cellulosic membrane is a generally homogeneous membrane. Inaccordance with a preferred embodiment of the invention, the membranefilter is characterized in that it has a pore size distribution having amedian pore size between 3 and 12 microns and having at least 40% of thepore volume being constituted by pores having a pore cross sectiondiameter of between 3 and 10 microns and having at least 5% of the porevolume being constituted by pores having a pore cross section diameterlarger than 10 microns. In accordance with a preferred embodiment of theinvention, no more than 60% of the pore volume is constituted by poreshaving a pore cross section diameter larger than 10 microns. Inaccordance with a preferred embodiment of the invention, the membranefilter is characterized in that at least 40% of its pore volume isconstituted by pores having a pore cross section diameter of between 3and 10 microns. In accordance with a preferred embodiment of theinvention, the membrane filter is characterized in that at least 5% ofthe pore volume is constituted by pores having a pore cross sectiondiameter larger than 10 microns. In accordance with a preferredembodiment of the invention, the membrane filter is characterized inthat no more than 30% of the pore volume is constituted by pores havinga pore cross section diameter less than 3 microns. In accordance with apreferred embodiment of the invention, the membrane filter ischaracterized in that at least 40% of its pore volume is constituted bypores having a pore cross section diameter of between 3 and 10 microns.In accordance with a preferred embodiment of the invention, the membranefilter is characterized in that at least 5% of the pore volume isconstituted by pores having a pore cross section diameter larger than 10microns. In accordance with a preferred embodiment of the invention, themembrane filter is characterized in that no more than 30% of the porevolume is constituted by pores having a pore cross section diameter lessthan 3 microns.

[0043] There is also provided in accordance with a preferred embodimentof the invention a leukocyte filtering method comprising: supplyingwhole blood to a prefilter; and supplying prefiltered whole blood to amembrane filter downstream of the prefilter, said membrane filter incharacterized in that it has a pore size distribution having a medianpore size between 3 and 12 microns and having at least 40% of the porevolume is constituted by pores having a pore cross section diameter ofbetween 3 and 10 microns and having at least 5% of the pore volume beingconstituted by pores having a pore cross section diameter larger than 10microns. In accordance with a preferred embodiment of the invention, nomore than 60% of the pore volume is constituted by pores having a porecross section diameter larger than 10 microns. In accordance with apreferred embodiment of the invention, the membrane filter ischaracterized in that at least 40% of its pore volume is constituted bypores having a pore cross section diameter of between 3 and 10 microns.In accordance with a preferred embodiment of the invention, the membranefilter is characterized in that at least 5% of the pore volume isconstituted by pores having a pore cross section diameter larger than 10microns. In accordance with a preferred embodiment of the invention, themembrane filter is characterized in that no more than 30% of the porevolume being constituted by pores having a pore cross section diameterless than 3 microns. In accordance with a preferred embodiment of theinvention, The membrane filter is characterized in that at least 40% ofits pore volume is constituted by pores having a pore cross sectiondiameter of between 3 and 10 microns. In accordance with a preferredembodiment of the invention, the membrane filter is characterized inthat at least 5% of the pore volume is constituted by pores having apore cross section diameter larger than 10 microns. In accordance with apreferred embodiment of the invention, the membrane filter ischaracterized in that no more than 30% of the pore volume beingconstituted by pores having a pore cross section diameter less than 3microns. In accordance with a preferred embodiment of the invention, themembrane filter is characterized in that at least 5% of the pore volumeis constituted by pores having a pore cross section diameter larger than10 microns. In accordance with a preferred embodiment of the invention,the membrane filter is characterized in that no more than 30% of thepore volume is constituted by pores having a pore cross section diameterless than 3 microns.

[0044] There is also provided in accordance with a preferred embodimentof the invention a leukocyte filtering method comprising: supplyingwhole blood to a prefilter; and supplying prefiltered whole blood to amembrane filter downstream of the prefilter, said membrane filter beingcharacterized in that at least 40% of its pore volume is constituted bypores having a pore cross section diameter of between 3 and 10 microns.In accordance with a preferred embodiment of the invention, the membranefilter is characterized in that at least 5% of the pore volume isconstituted by pores having a pore cross section diameter larger than 10microns. In accordance with a preferred embodiment of the invention, themembrane filter is characterized in that no more than 30% of the porevolume is constituted by pores having a pore cross section diameter lessthan 3 microns. In accordance with a preferred embodiment of theinvention, the membrane filter is characterized in that no more than 30%of the pore volume is constituted by pores having a pore cross sectiondiameter less than 3 microns. In accordance with a preferred embodimentof the invention, the membrane filter is characterized in that it has apore size distribution having a median pore size between 3 and 12microns and having at least 40% of the pore volume being constituted bypores having a pore cross section diameter of between 3 and 10 micronsand having at least 5% of the pore volume being constituted by poreshaving a pore cross section diameter larger than 10 microns. Inaccordance with a preferred embodiment of the invention, the membranefilter is characterized in that no more than 30% of the pore volume isconstituted by pores having a pore cross section diameter less than 3microns. In accordance with a preferred embodiment of the invention, themembrane filter is characterized in that it has a pore size distributionhaving a medium pore size between 3 and 12 microns and having at least40% of the pore volume being constituted by pores having a pore crosssection diameter of between 3 and 10 microns and having at least 5% ofthe pore volume being constituted by pores having a pore cross sectiondiameter larger than 10 microns. In accordance with a preferredembodiment of the invention, the membrane filter is characterized inthat it has a pore size distribution having a median pore size between 3and 12 microns and having at least 40% of the pore volume beingconstituted by pores having a pore cross section diameter of between 3and 10 microns and having at least 5% of the pore volume beingconstituted by pores having a pore cross section diameter larger than 10microns.

[0045] There is also provided in accordance with a preferred embodimentof the invention a leukocyte filtering method comprising: supplyingwhole blood to a prefilter; and supplying prefiltered whole blood to amembrane filter having at least 5% of its pore volume constituted bypores having a pore cross section diameter larger than 10 microns.

[0046] There is also provided in accordance with a preferred embodimentof the invention a leukocyte filtering method comprising: supplyingwhole blood to a prefilter; and supplying prefiltered whole blood to amembrane filter downstream of the prefilter, said membrane filter beingcharacterized in that no more than 30% of its pore volume is constitutedby pores having a pore cross section diameter less than 3 microns.

[0047] There is also provided in accordance with a preferred embodimentof the invention leukocyte filtered whole blood characterized in that:it includes (i) less than one million leukocytes per unit of blood, and(ii) at least one of; (a) at least sixty percent of the number ofplatelets in non-filtered whole blood; and (b) at least ninety percentof the number of red cells in non-filtered whole blood. In accordancewith a preferred embodiment of the invention, the leukocyte filteredwhole blood is characterized in that it includes: at least sixty percentof the number of platelets in non-filtered whole blood; and at leastninety percent of the number of red cells in non-filtered whole blood.In accordance with a preferred embodiment of the invention, theleukocyte filtered whole blood is produced by a method including:supplying whole blood to a prefilter which captures less than 60% ofincoming leukocytes; and supplying prefiltered whole blood to anon-cellulosic and generally homogeneous membrane filter. In accordancewith a preferred embodiment of the invention, the membrane filter ischaracterized in that it has a pore surface area/membrane volume ratiolarger than 6 square meters per milliliter of membrane volume. Inaccordance with a preferred embodiment of the invention, the membranefilter is characterized in that it has a pore surface area/membrane massratio larger than 12 square meters per gram of membrane. In accordancewith a preferred embodiment of the invention, the membrane filtercomprises at least one layer of a generally homogeneous non-cellulosicmembrane, wherein the total pore volume of pores having a diameterbetween 1-30 microns is less than 90% of the total pore volume. Inaccordance with a preferred embodiment of the invention, the membranefilter is characterized in that it has a pore size distribution having amedian pore size between 3 and 12 microns and having at least 40% of thepore volume being constituted by pores having a pore cross sectiondiameter of between 3 and 10 microns and having at least 5% of the porevolume being constituted by pores having a pore cross section diameterlarger than 10 microns. In accordance with a preferred embodiment of theinvention, no more than 60% of the pore volume is constituted by poreshaving a pore cross section diameter larger than 10 microns. Inaccordance with a preferred embodiment of the invention, the membranefilter is characterized in that at least 40% of its pore volume isconstituted by pores having a pore cross section diameter of between 3and 10 microns. In accordance with a preferred embodiment of theinvention, the membrane filter is characterized in that at least 5% ofthe pore volume is constituted by pores having a pore cross sectiondiameter larger than 10 microns. In accordance with a preferredembodiment of the invention, the membrane filter is characterized inthat no more than 30% of the pore volume being constituted by poreshaving a pore cross section diameter less than 3 microns. In accordancewith a preferred embodiment of the invention, the leukocyte filteredwhole blood is produced by a method comprising: supplying whole blood toa prefilter; and supplying prefiltered whole blood to a membrane filterdownstream of the prefilter, said membrane filter being characterized inthat it has a pore surface area/membrane volume ratio larger than 6square meters per milliliter of membrane volume. In accordance with apreferred embodiment of the invention, the leukocyte filtered wholeblood is produced by a method comprising: supplying whole blood to aprefilter; and supplying prefiltered whole blood to a membrane filterdownstream of the prefilter, said membrane filter being characterized inthat it has a pore surface area/membrane mass ratio larger than 12square meters per gram of membrane. In accordance with a preferredembodiment of the invention, the leukocyte filtered whole blood isproduced by a method comprising: supplying whole blood to a prefilter;and supplying prefiltered whole blood to a membrane filter downstream ofthe prefilter, said membrane filter being characterized in that it has apore size distribution having a median pore size between 3 and 12microns and having at least 40% of the pore volume being constituted bypores having a pore cross section diameter of between 3 and 10 micronsand having at least 5% of the pore volume being constituted by poreshaving a pore cross section diameter larger than 10 microns. Inaccordance with a preferred embodiment of the invention, the leukocytefiltered whole blood is produced by a method comprising: supplying wholeblood to a prefilter, and supplying prefiltered whole blood to amembrane filter downstream of the prefilter, said membrane filter beingcharacterized in that at least 40% of its pore volume is constituted bypores having a pore cross section diameter of between 3 and 10 microns.In accordance with a preferred embodiment of the invention, theleukocyte filtered whole blood is produced by a method comprising:supplying whole blood to a prefilter; and supplying prefiltered wholeblood to a membrane filter having at least 5% of its pore volumeconstituted by pores having a pore cross section diameter larger than 10microns. In accordance with a preferred embodiment of the invention, theleukocyte filtered blood product is produced by a method comprising:supplying whole blood to a prefilter; and supplying prefiltered wholeblood to a membrane filter downstream of the prefilter, said membranefilter being characterized in that no more than 30% of its pore volumeis constituted by pores having a pore cross section diameter less than 3microns.

[0048] There is also provided in accordance with a preferred embodimentof the invention leukocyte filtered whole blood produced by a methodincluding: supplying whole blood to a prefilter which captures less than60% of incoming leukocytes; and supplying prefiltered whole blood to anon-cellulosic and generally homogeneous membrane filter. In accordancewith a preferred embodiment of the invention, the membrane filter ischaracterized in that it has a pore surface area/membrane volume ratiolarger than 6 square meters per milliliter of membrane volume. Inaccordance with a preferred embodiment of the invention, the membranefilter is characterized in that it has a pore surface area/membrane massratio larger than 12 square meters per gram of membrane. In accordancewith a preferred embodiment of the invention, the membrane filtercomprises at least one layer of a generally homogeneous non-cellulosicmembrane, wherein the total pore volume of pores having a diameterbetween 1-30 microns is less than 90% of the total pore volume. Inaccordance with a preferred embodiment of the invention, the membranefilter is characterized in that it has a pore size distribution having amedian pore size between 3 and 12 microns and having at least 40% of thepore volume being constituted by pores having a pore cross sectiondiameter of between 3 and 10 microns and having at least 5% of the porevolume being constituted by pores having a pore cross section diameterlarger than 10 microns. In accordance with a preferred embodiment of theinvention, no more than 60% of the pore volume is constituted by poreshaving a pore cross section diameter larger than 10 microns. Inaccordance with a preferred embodiment of the invention, the membranefilter is characterized in that at least 40% of its pore volume isconstituted by pores having a pore cross section diameter of between 3and 10 microns. In accordance with a preferred embodiment of theinvention, the membrane filter is characterized in that at least 5% ofthe pore volume is constituted by pores having a pore cross sectiondiameter larger than 10 microns. In accordance with a preferredembodiment of the invention, the membrane filter is characterized inthat no more than 30% of the pore volume is constituted by pores havinga pore cross section diameter less than 3 microns.

[0049] There is also provided in accordance with a preferred embodimentof the invention leukocyte filtered whole blood produced by a methodcomprising: supplying whole blood to a prefilter; and supplyingprefiltered whole blood to a membrane filter downstream of theprefilter, said membrane filter being characterized in that it has apore surface area/membrane volume ratio larger than 6 square meters permilliliter of membrane volume.

[0050] There is also provided in accordance with a preferred embodimentof the invention leukocyte filtered whole blood produced by a methodcomprising: supplying whole blood to be filtered of leukocytes to aprefilter; and supplying prefiltered whole blood to a membrane filterdownstream of the prefilter, said membrane filter being characterized inthat it has a pore surface area/membrane mass ratio larger than 12square meters per gram of membrane.

[0051] There is also provided in accordance with a preferred embodimentof the invention leukocyte filtered whole blood produced by a methodcomprising: supplying whole blood to be filtered of leukocytes to aprefilter; and supplying prefiltered whole blood to a membrane filterdownstream of the prefilter, said membrane filter being characterized inthat it has a pore size distribution having a median pore size between 3and 12 microns and having at least 40% of the pore volume beingconstituted by pores having a pore cross section diameter of between 3and 10 microns and having at least 5% of the pore volume beingconstituted by pores having a pore cross section diameter larger than 10microns.

[0052] There is also provided in accordance with a preferred embodimentof the invention leukocyte filtered whole blood produced by a methodcomprising: supplying whole blood to a prefilter; and supplyingprefiltered whole blood to a membrane filter downstream of theprefilter, said membrane filter being characterized in that at least 40%of its pore volume is constituted by pores having a pore cross sectiondiameter of between 3 and 10 microns.

[0053] There is also provided in accordance with a preferred embodimentof the invention leukocyte filtered whole blood product produced by amethod comprising: supplying whole blood to a prefilter; and supplyingprefiltered whole blood to a membrane filter having at least 5% of itspore volume constituted by pores having a pore cross section diameterlarger than 10 microns.

[0054] There is also provided in accordance with a preferred embodimentof the invention leukocyte filtered whole blood produced by a methodcomprising: supplying whole blood to a prefilter; and supplyingprefiltered whole blood to a membrane filter downstream of theprefilter, said membrane filter being characterized in that no more than30% of its pore volume is constituted by pores having a pore crosssection diameter less than 3 microns.

[0055] In the context of the present application, the followingdefinitions are used throughout:

[0056] “Pore size” is pore diameter in microns or other units of length,calculated as a function of mercury intrusion pressure, assumingcylindrical pores and the appropriate value of mercury surface tensionand contact angle.

[0057] “Median pore size” is that pore size, above and below which thesame volume of mercury is pressed into the membrane, e.g. if the medianpore size is 10 microns, then the total amount mercury in all pores of asize less than 10 microns is the same as the total amount of mercury inall pores of a size greater than 10 microns.

[0058] “Pore size distribution” is the population frequency distributionof pores whose size is determined as described above.

[0059] “Cumulative pore volume” is the total mercury volume pressed intopores of a given size range.

[0060] “Symmetric membrane” and “homogeneous membrane” are usedsynonymously to refer to a membrane wherein most pores of the membranemaintain approximately the same pore cross sectional diameter along theentire length of the pore through the thickness of the membranestructure, irrespective of the pore size distribution in the membrane.

[0061] “Pore cross section diameter” (or “pore diameter”) is thediameter of the pore (assumed to be cylindrical) calculated as describedabove. “Pore size” and “pore diameter” are used synonymously throughoutthe present description and claims.

[0062] The present invention also seeks to provide a novel membraneleukoreduction filter, a filtering method and filtered blood products.The present inventors have found that contrary to teachings of the priorart, certain commercial membranes can be used to make efficientleukoreduction filters. Also simpler structures than previouslyconceived were found to make for highly efficient filters. These novelstructures comprise only two groups of layers, wherein individual layerswithin each group are generally identical (and need not have graduallyor step-wise diminishing pore sizes or be arranged to have gradually orstep-wise diminishing pore sizes). The first group acts as preliminaryfilter (prefilter), capturing gel particles, microaggregates and acertain fraction of the leukocytes. The second group of identical layerscaptures the remaining fraction of leukocytes.

[0063] The preliminary filter layer is typically made of no-woven sheetswith relatively large diameter fibers (3,5-10 microns in diameter),although woven sheets and membranes not necessarily of the samestructure as the filter membranes may also be employed for this purpose.The second layer is typically made of identical membrane sheets having amedian pore size of 3-12 microns. In contrast to the teachings of theprior art, it was found that the membranes do not need to have anespecially narrow pore size distributing (such as the total volume ofpores of 2-30 microns size constituting more than 94% of the total porevolume). It was also found, in contrast to the teaching of the priorart, that when used in accordance with the present invention, thenon-woven sheets can be made of relatively large diameter fibers (3.5-10microns vs. 1-3 microns as taught in the prior art). The filters of thepresent invention can be used without any post-treatment to filterpacked red cell units or whole blood. If it is desired to recoverplatelets from either whole blood or platelet concentrates, the membraneand prefilter can be chemically treated to provide media combiningefficient white cell retention and good platelet and red cell recover(e.g. by the method described in U.S. Pat. No. 5,783,094, the disclosureof which is incorporated herein by reference).

[0064] In a preferred embodiment of the present invention, the filter isconstructed of two groups of layers, each group containing generallyidentical layers of filter media. One group comprises non-cellulosicmembranes, while the other group comprises the prefilter material,preferably non-woven sheets.

[0065] The group of membranes can be made of any biocompatiblenon-cellulosic polymer composition. For example nylon, polyvinylchloride (PVC), PVC copolymers, polyvinylidene fluoride sulfenepolymers, polyester, polyketones, aromatic polyamides, polyimides,polycarbonate, polyphenylene oxide, polyvinyl acetate and the like canbe used to form the membranes of the present invention, The membranescan be manufactured by processes known in the art, including but notlimited to solution has separation, thermal inversion, foaming andsintering. Preferably, the thickness of each membrane is less than 0.25mm, preferably of thickness between about 0.05 mm and about 0.2 mm. Asanalyzed by mercury porosimetry, the membrane filter preferably has amedium pore size of 3.0-12 μm.

[0066] In contrast to the teachings of the prior art, pore sizedistribution does not need to be especially narrow. Typically, pores inthe range of 2-30 μm preferably constitute less than 94% of the totalpore volume of the membrane. Also, in contrast to the teachings of theprior art, in a preferred embodiment of the invention, the membrane isessentially symmetrical and isotropic, having homogeneous poresthroughout its bulk.

[0067] When a group of non=woven sheets is used in a prefilter or as aprefilter for the membrane, the group of sheets preferably has a meanfiber diameter larger than that necessary in filters of the prior art inwhich leukocytes are captured mostly by the non-woven material. The mostpreferred mean fiber diameter is 3.5-10 μm. The non-woven sheets can bemade of various biocompatible materials, e.g., polyester, nylon,polypropylene, cellulose derivatives and the like. It will beunderstood, however, that other materials can be used in theconstruction of the prefilter portion, such as woven sheets or membraneshaving a pore structure and/or pore size distribution not necessarilythe same as the pore structure or pore size distribution of themembranes used to construct the filter portion of the leukocyte filter.

[0068] Prior art methods for filtering blood, particularly whole blood,employ a prefilter, generally to prevent clogging of the filtermembranes. The prefilters of the prior art may themselves be layers ofmembranes, or they may be woven or non-woven sheets. However, contraryto the teachings of the prior art, in accordance with the presentinvention the thickness of the prefilter, whether a group of non-wovensheets or other material, will typically be more than 0.5 mm. Also, incontrast to the prior art, in the present invention the group ofpreliminary filter layers (whether fabricated from non-woven sheets orfrom other materials, such membranes different from the membrane orgroup of membranes used in the filter portion) can be made to captureless than 60% of all leukocytes, and the leukocyte filter will still behighly efficient in both leukocyte retention and volume recovery.

[0069] In constructing a leukocyte filter according to one preferredembodiment of the present invention, at least two membrane layers arestacked with at least two non-woven sheets and placed in an appropriatehousing made of biocompatible plastic. Whole blood or blood reactionsare allowed to flow through the filter by gravity. According to anotherpreferred embodiment of the present invention a single membrane layer isstacked with at least two layers of non-woven sheets to make a leukocytefilter.

[0070] The membrane and non-woven fabric layers can be either untreatedor treated. When untreated, whole blood and packed red cells can beefficiently leukoreduced. Platelets in whole blood are also retained bya filter so constructed. If it is desired to recover platelets fromeither whole blood or platelet-containing blood fractions, the filtermedia (both membrane and non-woven) need to be chemically treated toprevent blockage of the platelets. Such treatment can, although need notnecessarily be, in accordance with that described in U.S. Pat. No.5,783,094, assigned to the present applicant/assignees, the disclosureof which is incorporated herein by reference. Such treatment efficientlycoats all external and internal surfaces of the filter media and rendersthem platelet compatible. Physical and mechanical properties of themedia are not affected by the treatment.

BRIEF DESCRIPTION OF THE DRAWINGS

[0071] The present invention will be understood and appreciated morefully from the following detailed description, taken in conjunction withthe drawings in which:

[0072]FIG. 1 is a simplified concept-level illustration of a leukocytefilter constructed and operative in accordance with a preferredembodiment of the invention;

[0073]FIG. 2 is a simplified partially cut-away pictorial illustrationof a leukocyte filter of the type shown in FIG. 1, illustrating apreferred membrane structure useful therein;

[0074]FIGS. 3A and 3B are simplified pictorial illustrations ofrespectively a prior art membrane structure and a homogeneous membranestructure useful in the filter of FIGS. 1 & 2 in accordance with apreferred embodiment of the present invention;

[0075]FIG. 4 is a simplified pictorial illustration of a preferredmembrane structure useful in the filter of FIGS. 1 & 2 in accordancewith a preferred embodiment of the present invention; and

[0076]FIG. 5 is a simplified illustration of a preferred pore sizedistribution of a preferred membrane structure useful in the filter ofFIGS. 1 & 2 in accordance with a preferred embodiment of the presentinvention.

DETAILED DESCRIPTION OF A PREFERRED EMBODIMENT

[0077] Reference is now made in FIG. 1, which is a simplifiedconcept-level illustration of a leukocyte filter constructed andoperative in accordance with a preferred embodiment of the invention. Asseen in FIG. 1 there is provided a whole blood leukocyte filter 10typically comprising a filter housing 12 defining a whole blood inlet 14and a leukocyte-filtered blood outlet 16.

[0078] Disposed in filter housing 12 is a prefilter portion 18 anddownstream thereof a membrane filter portion 20. In accordance with apreferred embodiment of the present invention, the prefilter portion ischaracterized in that it captures less than 60% of incoming leukocytes,which are designated by reference numeral 22. The membrane filterportion 20 is preferably characterized in that it is non-cellulosic andgenerally homogeneous. Other whole blood components include red bloodcells, which are designated by reference numeral 24, platelets, whichare designated by reference numeral 26 and plasma, which is designatedby reference numeral 28.

[0079] Reference is now made to FIG. 2, which is a simplified partiallycut-away pictorial illustration of a leukocyte filter of the type shownin FIG. 1, illustrating a preferred membrane structure useful therein.For the sake of conciseness, the reference numerals employed in FIG. 1are also employed in FIG. 2 for equivalent elements thereof.

[0080] AS seen in FIG. 2, the membrane filter portion 20, downstream ofthe prefilter portion 18, is preferably characterized in that it has apore surface area/membrane volume ratio larger than 6 square meters permilliliter of membrane volume. The pore surface area, as seen in sectionin FIG. 2, is constituted by the interior surfaces 30 of the variouspores 32. The leukocytes 22 tend to adhere to interior surfaces 30 andare thus filtered out from the prefiltered whole blood supplied thereto.Preferably, the membrane filter portion is characterized in that it hasa pore surface area/membrane weight ratio larger than 12 square metersper gram of membrane.

[0081] Reference is now made to FIGS. 3A & 3B, which taken togetherillustrate another preferred feature of the present invention.Conventional leukocyte filters employ non-homogeneous membranes of thetype shown in FIG. 3A. The non-homogeneous membranes are generallycharacterized in that they have larger pore cross sections at theupstream region of the membrane than at the downstream region thereof.The use of non-homogeneous membranes involves significant costs.

[0082] It is a preferred feature of the present invention that themembrane filter portion 20 thereof preferably employs homogeneousmembranes, i.e. membranes which have upstream pore cross sections ofgenerally the same size as downstream pore cross sections. This providessignificant cost savings with substantially no degradation in filterquality. An example of such membranes is shown in FIG. 3B. As seen inFIG. 3B, in contrast to the membrane structure in FIG. 3A, the crosssections of the pores 32 may be larger or generally the same at thedownstream region of the membrane as compared with the cross sections ofthe pores at the upstream region thereof.

[0083] Reference is now made to FIG. 4, which is a simplified pictorialillustration of a preferred membrane structure useful in the filter ofFIGS. 1 & 2 in accordance with a preferred embodiment of the presentinvention. As seen in FIG. 4, a membrane filter portion 20, downstreamof the prefilter portion 18 is formed with at least some membrane layershaving pores that are “leaky”. By “leaky” is meant that the pore crosssection is such that normally some leukocytes 22 flow therethrough.Thus, application of an excessive load of leukocytes on any individualmembrane layer is avoided, thus reducing the likelihood of clogging. Byusing a group of membranes, good overall leukocyte filtering isnevertheless be achieved. While, as shown in FIG. 4, it is notnecessarily true that all pores in a membrane are leaky, it ispreferably true of some pores, such as the pore designated by referencenumeral 40.

[0084] In accordance with a preferred embodiment of the presentinvention, the membrane filter portion has a pore size distributionhaving a median pore size between 3 and 12 microns and having at least40% of the pore volume being constituted by pores having a pore crosssection diameter of between 3 and 10 microns. Preferably at least 5% ofthe pore volume is constituted by pores having a pore cross sectiondiameter larger than 10 microns.

[0085] Preferably, not more than 60% of the pore volume is constitutedby pores having a pore cross section diameter larger than 10 microns.

[0086] In accordance with a preferred embodiment of the presentinvention, the membrane filter portion includes at least one layer of agenerally homogeneous non-cellulosic membrane, wherein the total porevolume of pores in the membrane having a diameter between 1-30 micronsis less than 90% of the total pore volume.

[0087] In accordance with a preferred embodiment of the presentinvention, the membrane filter portion is characterized in that no morethan 30% of the pore volume is constituted by pores having a pore crosssection diameter less than 3 microns.

[0088] A preferred pore size distribution is illustrated in FIG. 5,which shows a pore distribution wherein at least 40% of the cumulative(total) volume of all pores is located in pores of 3-10 micronsdiameter, less than 30% of the cumulative volume of all pores is locatedin pores less than 3 micron diameter, and at least 5% of the cumulativevolume of all pores is located in pores of at least 10 microns diameter.

[0089] In accordance with one preferred embodiment of the presentinvention, a leukoreduction filter preferably includes at least onelayer of a non-cellulosic membrane with a median pore size of 3.0-12 μm,as determined by mercury porosimetry. The membrane is preferablysymmetric, i.e., there is preferably little difference in the size ofeach pore across the membrane thickness, irrespective of pore sizedistribution in the membrane. Each membrane layer preferably has athickness of less than about 0.25 mm, preferably between about 0.05 mmand about 0.2 mm.

[0090] Preferably, membranes employed in the present invention are“tortuous path membranes”, as contrasted to “track etched membranes”.Track etched membranes have generally cylindrical pores going straightthrough the thickness of the membrane. Track etched membranes, used insome prior art, often have very poor throughput.

[0091] An example of a commercially available membrane suitable for thepresent invention is “VERSAPOR”, a membrane made of a PVC-acrylonitrile(PVC-AN) copolymer and manufactured by Pall-Gelman, New York. Anotherexample is “NYLON MAGNA”, made by MSI-Osmonics, Massachusetts. The mostpreferred “Versapor” membrane has a median pore size of 5-5.5 microns,and the most preferred “Magna” membrane has a median pore size of4.5-5.5 microns. Surprisingly, the present inventors have found thatthese commercially available membranes, in combination with anappropriately chosen preliminary filter, satisfactorily filterleukocytes from blood. Nylon and PVC-acrylonitrile copolymer are verydifferent chemically. Since both types of membranes performsatisfactorily, it can be stated that chemical constitution is far lessimportant in the context of the present invention than pore structureand pore distribution. This is especially true when the membranes arechemically post-treated, rendering their surface chemical propertiesindependent of the chemistry of the base polymer.

[0092] A preferred median membrane pore size is 3-12 microns. A stillmore preferred median pore size is 5-9 microns. It was also found that apreferred pore size distribution is one wherein the pores between 2-10microns constitute 70-90% of the total pore volume of the membrane.

[0093] Preferably, the number of membrane layers in the filter rangesfrom 1 to 10.

[0094] Preferably stacked together with (but not bonded to) the layersof the membrane are at least two layers of a preliminary filtermaterial, preferably (but not necessarily) melt blown non-woven sheetswith a mean fiber size of 3.5-10 μm. The layers of the preliminaryfilter material serve as a prefilter for the layers of the membrane.When this material comprises non-woven sheets, the non-woven materialmay be made of various biocompatible materials, e.g., polyester, nylon,polypropylene, cellulose derivatives and the like. Woven sheets andmembranes not necessarily of the same structure as the membranes used asfilter material may also be used as the preliminary filter material.Preferably, the number of preliminary filter layers ranges from 2 toabout 30. The membrane layers and the preliminary filter materialtogether form a filter stack, which is preferably disposed in a housinghaving a blood inlet and an outlet.

[0095] Thus, whereas in the prior art membranes with high asymmetry oran especially narrow pore size distribution are employed, membranes ofthe present invention are non-cellulosic preferably symmetric membraneswith a median pore size of 3-12 microns. Also, whereas in the prior artmembranes with limited leukocyte capacity are used, requiring apreliminary filter capturing a majority of the leukocytes, membranes ofthe present invention enable the use of preliminary filters with lowercapacity.

[0096] The above described embodiment not only filters out leukocytes,it also generally blocks passage of platelets. In accordance withanother preferred embodiment of the present invention, the layers of themembrane and non-woven material are treated by a post-treatment, such asthat described in U.S. Pat. No. 5,783,094, which treatment impartshydroxylic functionality to the surfaces of the membrane and thenon-woven material. The layers thus treated pass, instead of block,platelets. In such as embodiment, the leukocyte filter can be used torecover platelets from whole blood or a platelet-containing bloodfraction.

[0097] Several illustrative examples of the present invention are nowdescribed.

EXAMPLE 1 Whole Blood Filter with Platelet Recovery—Nylon

[0098] Nylon membrane sheets (MAGNA, Osmonics), which constitute anexample of the type of membrane shown in FIG. 3B or FIG. 4, were surfacecoated by dipping into an aqueous hydroxypropyl cellulose solution asper U.S. Pat. No. 5,783,094. The membrane was then dried in an oven at80° C. for 1 hr. Non-woven polyester sheets (120 g/m², median fiber size4 μm) were treated likewise.

[0099] The treated membrane and non-woven sheets were cut into squaresof 10×10 cm. Four layers of membrane were stacked onto (but not bondedto) 20 layers of non-woven sheets and placed in a housing with a bloodinlet and an outlet, whereby to form a filter of the type shown in FIG.1.

[0100] A unit of anticoagulated whole human blood was connected to thehousing inlet and was filtered at a head of 60 cm, i.e. the blood wasplaced 60 cm above the filter. Filtration was complete in about 25 min.

[0101] Analysis of the filtrate showed a red cell recovery of 92%, aplatelet recovery of 77% and a residual white cell count of 0.6 million.

EXAMPLE 2 Pore Size Distribution of Nylon Membrane

[0102] The membrane of example 1 was subjected to mercury porosimetry.This analysis showed a median pore size of 5.2 micrometer. Total porevolume of pores of pore size between 1-30 micrometers was 89%. Totalpore volume of pore size between 3-10 micrometers was 81%. Total porevolume of pores of pore size larger than 10 micrometers was 7%. Totalpore volume of pores of pore size smaller than 3 micrometers was 12%.The specific surface area of the membrane was 25.8 m²/g. The porevolume/pore size distribution falls within the distribution shown inFIG. 5.

EXAMPLE 3 Whole Blood Filter with Platelet Recovery

[0103] A PVC-AN membrane (VERSAPOR, Pall-Gelman), which constitutes anexample of the type of membrane shown in FIG. 3B or FIG. 4, wassurface-treated as described in Example 1. Non-woven polyester wastreated likewise. The membrane and non-woven materials were cut intocircles of 3.5 cm in diameter. Five membrane circles were stacked onto18 non-woven circles and placed in a housing, whereby to form a filterof the type shown in FIG. 1. Sixty ml of whole blood were passed throughthe filter by gravity. Analysis of the filter showed a platelet recoveryof 76% and residual white cell count of 0.19 million.

EXAMPLE 4 Pore Size Distribution of PVC-AN Membrane

[0104] The membrane of Example 3 was analyzed by mercury porosimetry.The analysis showed a median pore size of 5.3 microns. Total pore volumeof pores between 3-10 microns was 79%. Total pore volume of pores largerthan 10 micrometers was 9%. Pore volume of pores smaller than 3micrometers was 12%. The specific surface area of the membrane was 14.1m²/g. The pore volume/pore size distribution falls within thedistribution shown in FIG. 5.

EXAMPLE 5 (Comparative) Whole Blood Filter with Platelet—PVC-An

[0105] The experiment was run in a mode similar to Example 3, exceptthat the membrane layers were interspersed among the non-woven layers.Platelet recovery was 66% and residual white cell count was 0.08million.

EXAMPLE 6 Whole Blood Filter without Platelet Recovery—Nylon

[0106] Nylon membranes constituting an example of the type of membranesshown in FIG. 3B or FIG. 4, and non-woven polyester sheets were used asin Example 1, except that they were not surface treated. Filter size wasas in Example 3. Sixty-three ml of whole blood were passed through thefilter. Analysis of the filtrate showed a red cell recovery of 76%, sameas the volume recovery, platelet passage of 4% and residual white cellcount of 0.04 million.

EXAMPLE 7 Platelet Concentrate Filter

[0107] Nylon membranes constituting an example of the type of membranesshown in FIG. 3B or FIG. 4, and polyester non-woven sheets were surfacetreated as described in Example 1. Four membrane layers were put on topof 18 layers of non-woven material, and the stack was scaled in ahousing, whereby to form a filter of the type shown in FIG. 1.Fifty-five of platelet concentrate were passed through the filter bygravity. Analysis of the filtrate showed a platelet recovery of 83% anda residual white cell count of 0.08 million. EXAMPLE 8

Single Membrane Filter

[0108] A nylon membrane constituting an example of the type of membraneshown in FIG. 3B or FIG. 4 and non-woven sheets were treated as inExample 1. One layer of membrane and 24 layers of non-woven materialwere placed in a housing, whereby to form a filter of the type shown inFIG. 1. Whole blood was filtered through the assembled filter. Thefiltrate contained 87% of the original platelet concentration and only0.3 million leukocytes.

EXAMPLE 9 Pore Size Distribution

[0109] The nylon membrane of Example 8 was subjected to pore sizedistribution analysis by mercury porosimetry. Total pore volume of poresof pore size between 1 and 30 micrometers was found to be 83%. Totalpore volume of pores of pore size between 3-10 micrometers was found tobe 59%. Total pore volume of pores of pore size larger than 10micrometers was 13%. Total pore volume of pores of pore size smallerthan 3 micrometers was 28%. The specific surface area of the membranewas 25.6 m²/g. The pore volume/pore size distribution falls within thedistribution shown in FIG. 5.

[0110] It will be appreciated by persons skilled in the art that thepresent invention is not limited by what has been particularly shown anddescribed hereinabove. Rather the scope of the present inventionincludes both combinations and subcombinations of the various featuresdescribed hereinabove as well as variations and modifications whichwould occur to persons skilled in the art upon reading the specificationand which are not in the prior art.

1. A leukocyte filter comprising: a prefilter portion; and a membranefilter portion downstream of the prefilter portion, said membrane filterportion having a pore size distribution having a median pore sizebetween 3 and 12 microns and having at least 40% of the pore volumebeing constituted by pores having a pore cross section diameter ofbetween 3 and 10 microns and having at least 5% of the pore volume beingconstituted by pores having a pore cross section diameter larger than 10microns.